WIRELESS MAGNETO-MECHANICAL CONTROL OF NEURAL ACTIVITY MEDIATED BY MAGNETIC NANODISCS

磁性纳米圆盘介导的神经活动的无线磁机械控制

• 批准号: 10644156
• 负责人: Gabriela Romero Uribe
• 金额: $ 53.08万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-09 至 2024-09-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10644156
• 关键词: Acoustics; Adoption; Affective; Amygdaloid structure; Anxiety Disorders; Area; Auditory; Auditory area; Behavior; Behavioral; Biological; Biomedical Research; Brain; Brain Mapping; Calcium ion; Cell membrane; Cells; Cerebral cortex; Cerebrum; Complex; Deep Brain Stimulation; Deposition; Development; Discrimination; Electric Conductivity; Electric Stimulation; Emotional; Ensure; Evaluation; Fluo 4; Frequencies; Fright; Glutamates; Goals; Heating; Hyperthermia; Immune system; In Vitro; Lateral; Learning; Liquid substance; Magnetic nanoparticles; Magnetism; Malignant Neoplasms; Mechanical Stimulation; Mechanics; Mediating; Membrane; Mental disorders; Modeling; Mus; Nanostructures; Nervous system structure; Neuronal Dysfunction; Neurons; Output; Patch-Clamp Techniques; Pathway interactions; Pharmaceutical Preparations; Pharmacotherapy; Polyethylene Glycols; Production; Property; Rattus; Reporting; Research; Role; Scheme; Signal Transduction; Social Interaction; Specificity; Stimulus; Surface; System; Techniques; Technology; Testing; Tissues; Transcranial magnetic stimulation; Transducers; Transgenes; anxiety-related disorders; base; biomaterial compatibility; blood-brain barrier permeabilization; cell type; clinical practice; cost effective; cytotoxicity; design; extracellular; fluorescence imaging; implantable device; improved; in vitro activity; in vivo; insight; lithography; magnetic field; mechanical force; mechanical properties; mechanical stimulus; mind control; minimally invasive; nanodisk; nanomaterials; nanoscale; nervous system disorder; neural circuit; neural network; neural repair; neuroregulation; new therapeutic target; novel; optogenetics; patch clamp; plasmonics; receptor; relating to nervous system; remote control; response; side effect; sound; success; theranostics; therapy design; wireless

WIRELESS MAGNETO-MECHANICAL CONTROL OF NEURAL ACTIVITY MEDIATED BY MAGNETIC NANODISCS PROJECT SUMMARY / ABSTRACT Cell-type specific manipulation of neural circuits is required for the treatment of neurological disorders and psychiatric conditions. Precise control of neural circuits will enable the development of neuromodulation therapies for these debilitating conditions. Existing technologies to control neural activity offer limited possibilities. Manipulation of brain circuits via direct drug treatment is restricted by the selective permeability of the blood- brain barrier, the rapid clearance of cerebral fluids and the lack of specificity which results in poor response to drugs and undesirable side effects. Electrical stimulation and optogenetics have open the possibility of repairing neural dysfunction through direct control of brain circuit dynamics. However, both technologies require implantable devices that are damaging to biological tissues. Minimally invasive control of cell signaling with magnetic fields is being explored in basic studies of the nervous and immune systems. Wireless schemes based on hysteretic heating of magnetic nanoparticles in high frequency alternating magnetic fields (AMFs) have already permitted modulation of neural activity and cancer theranostics in vivo. Despite these advances, the potential off-target heating effects and challenges in scaling of high-frequency AMFs apparatuses impede universal adoption of magnetic hyperthermia in biomedical research. Here we propose a scalable magneto- mechanical scheme for remote control of neural activity mediated by magnetic nanodiscs (MNDs). MNDs will be fabricated by interference lithography and template-assisted physical deposition technique to produce in bulk non-toxic MNDs with high colloidal stability. When interfaced with the cell membranes, MNDs will act as transducers of low frequency low amplitude (20-50 mT, 5-10 Hz) magnetic fields into mechanical forces. This technology will be applied in vitro to control neural activity in cortical neurons isolated from rat brains. Moreover, we will investigate our technology to evoke auditory-driven fear behavior in mice by modulating neural activity in the auditory cortex → amygdala pathway. Modulation of auditory cortex to amygdala brain circuits could allow the development of non-invasive therapies for the management of fear and anxiety-related disorders. In contrast to magneto-thermal approaches, the system proposed here offers straightforward scalability to large volumes, requires significantly lower magnetic energy, and is capable of modulating cell activity without reliance on transgenes.

神经活动的无线电机械控制 磁性纳米盘介导的 项目总结/摘要 神经回路的细胞类型特异性操纵是治疗神经病症所必需的， 精神状况神经回路的精确控制将使神经调节的发展成为可能 治疗这些使人衰弱的疾病。控制神经活动的现有技术提供了有限的可能性。 通过直接药物治疗来操纵大脑回路受到血液选择性渗透性的限制- 脑屏障，脑液的快速清除和缺乏特异性，导致对 药物和不良副作用。电刺激和光遗传学为修复提供了可能 通过直接控制脑回路动力学而导致神经功能障碍。然而，这两种技术都需要 对生物组织造成损害的可植入装置。细胞信号转导的微创控制， 在神经系统和免疫系统的基础研究中正在探索磁场。基于无线方案 磁纳米粒子在高频交变磁场（AMF）中的滞后加热研究， 已经允许在体内调节神经活动和癌症治疗诊断。尽管取得了这些进展， 潜在的偏离目标的加热效应和高频AMF设备的缩放挑战阻碍了 磁热疗在生物医学研究中的普遍采用。在这里，我们提出了一个可扩展的磁电机- 通过磁性纳米盘（MND）介导的神经活动的远程控制的机械方案。MND将是 通过干涉光刻和模板辅助物理沉积技术来批量生产 具有高胶体稳定性的无毒MND。当与细胞膜连接时，MND将充当 将低频低振幅（20-50 mT，5-10 Hz）磁场转换为机械力。这 这项技术将在体外应用于控制从大鼠大脑中分离出来的皮层神经元的神经活动。此外，委员会认为， 我们将研究我们的技术，通过调节小鼠的神经活动， 听觉皮层→杏仁核通路。调节听觉皮层到杏仁核的脑回路 开发用于管理恐惧和焦虑相关疾病的非侵入性疗法。相比之下 对于磁热方法，这里提出的系统提供了对大体积的直接可缩放性， 需要显著更低的磁能，并且能够调节细胞活性而不依赖于 转基因